Macrophages regulate meiotic initiation and germ cell clearance in the developing ovary

Area of Science:

• Reproductive immunology
• Developmental biology
• Cellular and molecular biology

Background:

• Tissue-resident macrophages play key roles in organogenesis, but their function in fetal ovarian development is not well understood.
• The ontogeny of ovarian macrophages and their relationship with germ cell development and meiosis initiation are largely unknown.

Purpose of the Study:

• To map the multi-wave seeding and remodeling of ovarian macrophages during fetal and early postnatal development.
• To investigate the functional roles of ovarian macrophages in ovarian morphogenesis, germ cell meiosis, and oocyte reserve establishment.

Main Methods:

• Temporally-controlled lineage tracing of yolk-sac erythro-myeloid progenitors, fetal HSC-derived progenitors, and postnatal monocytes.
• Identification of macrophage subsets using MHCII and CSF1R markers.
• CCR2-dependent monocyte recruitment analysis.
• Macrophage depletion studies using CSF1R inhibition.

Main Results:

• Three major resident ovarian macrophage subsets with distinct kinetics and persistence were identified.
• CCR2-dependent monocyte recruitment is essential for postnatal macrophage maturation.
• Depletion of fetal macrophages impaired ovarian vascular growth and induced precocious meiotic initiation.
• Extended macrophage depletion disrupted perinatal germ cell attrition, despite postnatal repopulation.

Conclusions:

• Ovarian macrophages act as stage-specific regulators of ovarian development.
• These immune cells link immune ontogeny with ovarian morphogenesis and germ cell quality control.
• Macrophages are critical for establishing the oocyte reserve and ensuring proper timing of germ cell meiosis.